The star shot to fame playing the poetry writing anarchist Rick in The Young Ones, and enjoyed a glittering career which saw him appear in Britain's best-loved shows including Blackadder and Bottom.
It is not yet known what caused Mayall's unexpected death, and the world of comedy took to Twitter to lament a legend lost "too soon".
In the 1980s Mayall was part of the Comic Strip, a hugely influential group of alternative young comics that included Dawn French, Jennifer Saunders and Mayall's writing and performing partner, Adrian Edmondson.
On television he memorably played Conservative politician Alan B'stard in the sitcom "The New Statesman" and lecherous Lord Flashheart in comedy classic "Blackadder."
He and Edmondson also created and starred in "Bottom," a surreally violent slapstick series about two unemployed slobs.
Film appearances included the title role in 1991 fantasy "Drop Dead Fred" — which gained him a U.S. cult following — and 1999 British comedy "Guest House Paradiso."
"There were times when Rik and I were writing together when we almost died laughing," Edmondson said. "They were some of the most carefree, stupid days I ever had, and I feel privileged to have shared them with him. And now he's died for real. Without me. Selfish bastard."
The cause of death was not immediately disclosed. London's Metropolitan Police force said officers had been called to the house by the ambulance service on Monday, but that the death was not believed to be suspicious.
In 1998 Mayall was on life support and in a coma for several days after an all-terrain vehicle accident.
"The main difference between now and before my accident is I'm just very glad to be alive," Mayall said last year.
"Other people get moody in their forties and fifties - men get the male menopause. I missed the whole thing. I was just really happy."
Scotland Yard said police were called to Rik’s home in Barnes, South West London, by an ambulance crew after he collapsed. A spokesman said: “A man, aged in his 50s, was pronounced dead at the scene.”